The evolution of the TOR pathway and its role in cancer

E. M. Beauchamp, L. C. Platanias*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

93 Scopus citations

Abstract

The target of rapamycin (TOR) pathway is highly conserved among eukaryotes and has evolved to couple nutrient sensing to cellular growth. TOR is found in two distinct signaling complexes in cells, TOR complex 1 (TORC1) and TOR complex 2 (TORC2). These complexes are differentially regulated and act as effectors for the generation of signals that drive diverse cellular processes such as growth, proliferation, protein synthesis, rearrangement of the cytoskeleton, autophagy, metabolism and survival. Mammalian TOR (mTOR) is very important for development in embryos, while in adult organisms it is linked to aging and lifespan effects. In humans, the mTOR pathway is implicated in the tumorigenesis of multiple cancer types and its deregulation is associated with familial cancer syndromes. Because of its high biological relevance, different therapeutic strategies have been developed to target this signaling cascade, resulting in the emergence of unique pharmacological inhibitors that are either already approved for use in clinical oncology or currently under preclinical or clinical development. Multimodal treatment strategies that simultaneously target multiple nodes of the pathway and/or negative feedback regulatory loops may ultimately provide the best therapeutic advantage in targeting this pathway for the treatment of malignancies.

Original languageEnglish (US)
Pages (from-to)3923-3932
Number of pages10
JournalOncogene
Volume32
Issue number34
DOIs
StatePublished - Aug 22 2013

Keywords

  • Cancer
  • Leukemia
  • mTOR

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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